After his Russian opponent broke to lead 4-3 in the final set, Tsitsipas, who had already received a coaching warning and time violation, did not take kindly to being told to speed things up by French chair umpire Damien Dumusois.
"You are the worst. For some reason, you have something against me, I don't know what. Because you're French probably. And you're all weirdos. You're all weirdos," the 21-year-old shouted.
"Give me warning, I don't care. Give me warning, give me warning, yeah, give me warning, I don’t care. Give me warning!"
The eighth seed, who battled leg cramps during the final set, got what he asked for and given it was his second time violation of the match, it came with a point penalty.
The subsequent 6-4 6-7(5) 7-6(7) 7-5 loss meant Tsitsipas has now fallen at the first hurdle in three successive tournaments.
"I feel like I'm doing the same thing over and over again, and my brain can't really take it anymore," said Tsitsipas.
"I feel like I'm doing the same routines on the court, the same execution, the same -- I mean, same strategies and everything.
"And I feel like my mind is just -- I don't feel inspired. I play out on the court, and I don't feel like I'm chasing something."
Tsitsipas reached the Australian Open semi-finals in January but since falling in the first round at Wimbledon last month appears to have lost his way.
"I don't think he's necessarily uninspired, it's more that he's a little confused, that's my feeling from the outside," said former world number two and Eurosport analyst Alex Corretja.
After an ongoing dialogue with the umpire throughout the first four sets, Tsitsipas started to unravel when he was issued a warning for coaching.
Tsitsipas said his father and coach Apostolos had offered only words of encouragement and conceded that the coaching violation had thrown him off his stride.
"It's not very pleasant when you have the umpire give you warnings and time violations and coaching violations during a match. It can affect your thinking. It can affect your decision making," said Tsitsipas.
"I don't know what this chair umpire has in specific against my team but he's been complaining and telling me that my team talks all of the time when I'm out on the court playing," he added.
"He's very - I don't know. I believe he's not right, because I never hear anything of what my team says from the outside."